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Biomedical subjects

Y Aoyagi

Publications and source records attributed to Y Aoyagi.

At least 127 records · Page 7Linked to original sources

Sequence analysis of the proximal promoter region of the human alpha-fetoprotein gene in hepatocellular carcinoma.

We have examined whether or not mutations exist in the proximal promoter region of the human alpha-fetoprotein (AFP) gene in the hepatocellular carcinoma (HCC) tissue. Genomic DNA was extracted from four patients: one HCC tissue, one HCC and its corresponding non-cancerous (cirrhosis) tissues, one liver cirrhosis (LC) tissue without HCC and one matching HCC tissue and peripheral blood leukocytes. Serum concentrations of AFP in the patients ranged from less than 5 to 10,138 ng/ml. Nucleotide sequence was determined by direct sequencing using a single-stranded DNA template that was produced first through the polymerase chain reaction (PCR) amplification and then asymmetric PCR. In one HCC tissue taken from the patient with a high concentration of serum AFP, nucleotides different from published ones were detected at -120 and -113. These changes, however, probably reflect a DNA polymorphism, because peripheral blood leukocytes of the same patient had the same changes. Including this patient, no mutations in the region from -160 to -10 were detected in the HCC specimens we have examined. These results suggest that the extremely proximal promoter region of the AFP gene where glucocorticoid-responsive element and HNF-1 binding sites exist is not responsible for the re-expression of AFP in HCC.

Adult↗

Effects of training and acclimation on heat tolerance in exercising men wearing protective clothing.

This study examined the effectiveness of endurance training and heat acclimation in reducing the physiological strain imposed by exercising in the heat while wearing protective clothing. Seven young men underwent 8 weeks of physical training [60-80% maximal aerobic power (VO2max) for 30-45 min.day-1, 3-4 days.week-1 at < 25 degrees C] followed by 6 days of heat acclimation (45-55% VO2max for 60 min.day-1 at 40 degrees C, 30% relative humidity). Nine other young men underwent corresponding periods of control observation and heat acclimation. Before and after each treatment, subjects completed a treadmill walk (4.8 km.h-1, 2% grade) in a climatic chamber (40 degrees C, 30% relative humidity), wearing in turn normal combat clothing or clothing protecting against nuclear, biological, and chemical (NBC) agents. Criteria for halting this test were: (1) a rectal temperature (T(re)) of 39.3 degrees C; (2) a heart rate (fc) > or = 95% of the subject's observed maximum, maintained for 3 min; (3) unwillingness of the subject to continue; (4) the elapse of 120 min. The training regimen increased mean VO2max by 16% and mean plasma volume by 8%. When tested in normal combat clothing, the rates of increase in T(re) and fc were slower after training. However, when wearing NBC protective clothing, the only significant change induced by training was a higher mean skin temperature (Tsk) in the early part of the test. Heat acclimation increased the mean plasma volume of untrained subjects by 8%, but their VO2max remained unchanged. When tested in normal combat clothing, acclimation decreased their mean values of T(re), Tsk, fc, and metabolic rate. When wearing NBC protective clothing, the only significant decrease after acclimation was in overall T(re). In trained subjects, heat acclimation induced no further improvement in any physiological variable when wearing normal combat clothing, but reduced overall T(re) and Tsk when wearing NBC protective clothing. Training- or acclimation-induced increases of sweat secretion (an average increment of 0.14-0.23 kg.h-1) were not accompanied by any statistically significant increase in sweat evaporation when wearing NBC protective clothing. Moreover, tolerance times were unchanged in either normal combat (116-120 min) or NBC protective clothing (47-52 min). We conclude that neither endurance training nor heat acclimation do much to improve exercise tolerance when wearing NBC protective clothing in hot environments, because any added sweat secretion decreases blood volume and increases discomfort without augmenting body cooling.

Acclimatization↗

Progression and regression of atherosclerotic findings in the descending thoracic aorta detected by enhanced computed tomography.

Reports evaluating the progression and regression of atherosclerosis by non-invasive procedure are still limited. We investigated the progression and regression of atherosclerotic intimal thickening of the descending thoracic aorta non-invasively measured by enhanced computed tomography in 83 patients (average age 51.0 years) at the beginning and end of a 2.5 year period. The patients were not taking anti-hypertensive, lipid-lowering or hypoglycemic drugs and therefore we consider them as a natural history cohort. At entry, the extent of aortic intimal thickening was 35.2% of the circumference of the cross-section of the wall, which increased to 39.7% after 2.5 years. Spontaneous progression was associated directly with age, elevated levels of total cholesterol, LDL-cholesterol, LDL/HDL cholesterol ratio, diastolic blood pressure, and inversely to HDL-cholesterol. There was little correlation with triglycerides, systolic blood pressure, fasting glucose or body mass index. In 65 of the patients, aortic atherosclerosis progressed, while in 9 patients it remained unchanged, and in a further 9 it regressed. The levels of lipid variables, apart from HDL-cholesterol, and diastolic blood pressure in the patients with spontaneous progression were significantly higher than in the unchanged and spontaneous regression. Thus, this study verified the natural history of aortic atherosclerosis non-invasively measured by enhanced CT.

Adult↗

Highly enhanced fucosylation of alpha-fetoprotein in patients with germ cell tumor.

BACKGROUND: We have recently reported that simultaneous determination of the fucosylation and glucosaminylation of alpha-fetoprotein (AFP) was useful in the differential diagnosis of various liver diseases. Here, we measured these indices in germ cell tumor and compared them with those in various diseases to reveal the characteristic feature of the carbohydrate moiety of AFP in this tumor. METHODS: Fucosylation and glucosaminylation indices of AFP were determined for 743 serum samples from 10 patients with germ cell tumor, 437 with hepatocellular carcinoma (HCC), 241 with benign liver diseases (24 patients with acute viral hepatitis, 99 with chronic hepatitis, and 118 with hepatic cirrhosis), and 55 with carcinoma metastatic to the liver from digestive organs (41 from stomach, 10 from gallbladder, 2 from pancreas, and 2 from colon) by crossed immunoaffinoelectrophesis in the presence of concanavalin A and Lens culinaris agglutinin. RESULTS: The fucosylation index of AFP in germ cell tumors (99% +/- 2%, mean +/- SD) was higher than those in HCC (39% +/- 31%), carcinoma metastatic to the liver (76% +/- 27%), and benign liver diseases (4% +/- 7%); the differences were statistically significant (P < 0.001). The glucosaminylation index of AFP in germ cell tumor (45% +/- 20%) also was significantly higher than those in HCC (4% +/- 4%) and in benign liver diseases (1% +/- 4%) (P < 0.001). The difference in mean percentage of the glucosaminylation index, however, was not significant between germ cell tumors (45% +/- 20%) and carcinoma metastatic to the liver (39% +/- 23%). CONCLUSIONS: The current study indicates that the most characteristic feature of glycosylation of AFP in germ cell tumors is fucosylation rather than glucosaminylation.

Adolescent↗

Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma.

Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation.

Carbohydrate Metabolism↗

Phase IV group study of natural human interferon alpha (HLBI) on chronic myelogeneous leukaemia.

Under the control of Kanagawa CML/HLBI phase IV study group in Japan, 18 cases out of registered 30 cases of chronic myelogeneous leukaemia consisting of 17 chronic phase and 1 accelerated phase, during July, 1991 to January, 1992, were analyzed for their hematological responses and cytogentic responses preliminarily. Hematological response rate (PR + CR) was 83.3% including 50.0% of CR, as judged by Kimura's criteria after treatment with HLBI alone (16 cases) or/and with other chemotherapy (2 cases). The dosage and duration of HLBI therapy required to get into the complete remission ranged from 212 to 1272 millions IU and between 6 to 42 weeks (mean value was 20 weeks), respectively. The clonally proliferated leukocytes and decreased physiological hematopoiesis started to recover from 2 to 4 weeks and reached their normal ranges from 16 weeks after 6 millions IU of HLBI were administered every day. In the 4 cases examined, 3 cases showed minimal cytogenetic responses and a case showed no cytogenetic response. Slight and temporary adverse effects were observed in 15 out of 18 cases (83.3%) including fever, general malaise, appetite loss, eruption, diarrhea, glossitis, hypogustation, weight loss and local muscle pain.

Adult↗

Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans.

Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. Using reversed-phase and size-fractionation high performance liquid chromatography systems we identified six pyridylamino-sugar chains. The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. Thus, the fucosylated and non-fucosylated triantennary sugar chains were newly identified in human AFP. Essentially identical results were obtained for AFP from the patient with gallbladder carcinoma which metastasizes to the liver. These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver.

Carbohydrate Conformation↗

Fucosylation index of alpha-fetoprotein, a possible aid in the early recognition of hepatocellular carcinoma in patients with cirrhosis.

We report here on three patients with cirrhosis for whom an early recognition of hepatocellular carcinoma was made possible by the measurement of the degree of fucosylation (fucosylation index) of alpha-fetoprotein. Increased levels of this index associated with a moderate increment of serum concentration of alpha-fetoprotein were observed in three patients with cirrhosis who showed no indication of hepatocellular carcinoma by several imaging modalities. Four years after the onset of an increase in the fucosylation index, small hepatocellular carcinoma with a tumor diameter less than 2 cm was revealed in case 1. In cases 2 and 3, small hepatocellular carcinomas were detected 24 mo and 9 mo, respectively, after the first sign of the increase in the index. However, the development to hepatocellular carcinoma was not detected in five patients with cirrhosis in whom continuous increments of serum concentration of alpha-fetoprotein with low levels of fucosylation index were observed during the prospective follow-up from 3 to 9 yr. These findings indicated that the fucosylation index of alpha-fetoprotein can be used as an aid in an early recognition of hepatocellular carcinoma, especially in patients with cirrhosis during the follow-up process in which the moderate increment of serum concentration of alpha-fetoprotein is noted.

Carcinoma, Hepatocellular↗

Evaluation of morphological changes of the atherosclerotic aorta by enhanced computed tomography.

Enhanced and non-enhanced computed tomography (CT) were performed in 405 subjects (222 men; 183 women; mean age 57 years). Intimal atherosclerotic changes of the aorta were quantified by enhanced CT, revealing the atheromatous intima to be projecting and thick-walled, while non-enhanced CT demonstrated aortic calcification. We measured the degree of aortic intimal changes at various segments of the aorta. In 224 cases, CT was performed from the aortic root to the bifurcation of the abdominal aorta. Intimal changes were found predominantly at the aortic arch, the middle descending thoracic and the infrarenal abdominal aorta. As for the intimal changes, aortic calcification and aortic pulse wave velocity were significant atherosclerotic characteristics. The aortic diameter did not show a significant association with intimal change. Among the various atherosclerotic risk factors, intimal change was significantly associated with age, systolic blood pressure, serum total cholesterol and diabetes mellitus, whereas gender, diastolic blood pressure, relative weight and cigarette use were not significantly related. For coronary artery disease and arteriosclerosis obliterans, aortic intimal changes constituted a significant atherosclerotic feature. In cerebrovascular disease, however, aortic intimal change did not play a significant role.

Adolescent↗

A case of cyclophosphamide-induced interstitial pneumonitis diagnosed by bronchoalveolar lavage.

A successfully treated case of cyclophosphamide pneumonitis, which developed during treatment for a leukemic phase of B-cell non-Hodgkin's lymphoma, is documented. Subtyping of lymphocytes in the peripheral blood and the bronchoalveolar lavage fluid easily excluded a possible diagnosis of pulmonary involvement of lymphoma. Bronchoalveolar lavage is a useful approach to determine the correct etiology of pneumonitis.

Aged↗

Aging and muscle function.

Most of the available data on the aging of muscle function are cross-sectional in type. Static and dynamic muscle strength seem well preserved to about 45 years of age, but performance deteriorates by about 5% per decade thereafter. There is a parallel loss of lean tissue. Because muscle biopsy specimens are not always representative of an entire muscle, it is unclear whether there is a general hypotrophy or atrophy of the muscle fibres or a selective hypoplasia and degeneration of type II fibres associated with a loss of terminal sprouting. Other influences may include a deterioration of end-plate structures with impaired excitation-contraction coupling and impaired fibre recruitment. Both contraction time and half-relaxation time are prolonged with aging, and there is a decrease of maximal contraction velocity, more marked in the legs than in the arms. On the other hand, endurance at a fixed fraction of maximal force is increased. Potential factors leading to the enhanced endurance include a poorer maximal effort and an increased proportion of type I fibres; however, there is little evidence that muscle capillarity is altered. The loss of function is generally less in the arms than in the legs, but it remains unclear whether this is an inherent biological difference, or merely a reflection of differential changes in activity patterns between the upper and the lower limbs. The male/female strength ratio does not seem to change with age, but substantial slowing or reversal of the aging process is possible through appropriate activity programmes. The preservation of muscle function has important implications for the quality of life in the frail elderly, counteracting dyspnoea, stabilising joints and extending the period of independent living by up to 20 years.

Aging↗